Thymic stromal cells: Roles in atrophy and age-associated dysfunction of the thymus

Atrophy of the thymus, the primary site of T lymphocyte generation, is a hallmark of the aging immune system. Age-associated thymic atrophy results in diminished output of new, naïve T cells, with immune sequelae that include diminished responses to novel pathogenic challenge and vaccines, as well as diminished tumor surveillance. Although a variety of stimuli are known to regulate transient thymic atrophy, mechanisms governing progressive age-associated atrophy have been difficult to resolve. This has been due in part to the fact that one of the primary targets of age-associated thymic atrophy is a relatively rare population, thymic stromal cells. This review focuses on changes in thymic stromal cells during aging and on the contributions of periodic, stochastic, and progressive causes of thymic atrophy.